scholarly journals The High Mobility Group (Hmg) Boxes of the Nuclear Protein Hmg1 Induce Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells

2001 ◽  
Vol 152 (6) ◽  
pp. 1197-1206 ◽  
Author(s):  
Bernard Degryse ◽  
Tiziana Bonaldi ◽  
Paola Scaffidi ◽  
Susanne Müller ◽  
Massimo Resnati ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Muscle Cells ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Cytoskeleton Reorganization ◽  
Mitogen Activated Protein

HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a Gi/o protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.

Src-Dependence and Pertussis-Toxin Sensitivity of Urokinase Receptor-Dependent Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 649-662 ◽  
Author(s):  
Bernard Degryse ◽  
Massimo Resnati ◽  
Shafaat A. Rabbani ◽  
Antonello Villa ◽  
Francesca Fazioli ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Cell Shape ◽  
Muscle Cells ◽  
Soluble Form ◽  
Integrin Subunit ◽  
Cytoskeleton Reorganization

The catalytically inactive precursor of urokinase-type plasminogen activator (pro-u-PA) induced a chemotactic response in rat smooth muscle cells (RSMC) through binding to the membrane receptor of urokinase (u-PA receptor [u-PAR]). A soluble form of u-PAR activated by chymotrypsin cleavage as well as a peptide located between domain 1 and 2 of u-PAR reproduced the effect of pro-u-PA on cell migration. The chemotactic pro-u-PA effect correlates with a dramatic reorganization of actin cytoskeleton, of adhesion plaques, and with major cell shape changes in RSMC. Pro-u-PA induced a decrease in stress fiber content, membrane ruffling, actin ring formation, and disruption leading to the characteristic elongated cell shape of motile cells with an actin semi-ring located close to the leading edge of cells. u-PAR effects on both chemotaxis and cytoskeleton were sensitive to pertussis toxin and, hence, possibly require G proteins. u-PAR effects are accompanied by a relocation of u-PAR, vitronectin receptor (VNR) vβ3, β1 integrin subunit, and Src tyrosine kinase to the leading membrane of migrating cells. In conclusion, our data show that pro-u-PA, via binding to u-PAR, controls a signaling pathway, regulated by tyrosine kinases and possibly G proteins, leading to cell cytoskeleton reorganization and cell migration.

Src-Dependence and Pertussis-Toxin Sensitivity of Urokinase Receptor-Dependent Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 649-662 ◽  
Author(s):  
Bernard Degryse ◽  
Massimo Resnati ◽  
Shafaat A. Rabbani ◽  
Antonello Villa ◽  
Francesca Fazioli ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Cell Shape ◽  
Muscle Cells ◽  
Soluble Form ◽  
Integrin Subunit ◽  
Cytoskeleton Reorganization

Abstract The catalytically inactive precursor of urokinase-type plasminogen activator (pro-u-PA) induced a chemotactic response in rat smooth muscle cells (RSMC) through binding to the membrane receptor of urokinase (u-PA receptor [u-PAR]). A soluble form of u-PAR activated by chymotrypsin cleavage as well as a peptide located between domain 1 and 2 of u-PAR reproduced the effect of pro-u-PA on cell migration. The chemotactic pro-u-PA effect correlates with a dramatic reorganization of actin cytoskeleton, of adhesion plaques, and with major cell shape changes in RSMC. Pro-u-PA induced a decrease in stress fiber content, membrane ruffling, actin ring formation, and disruption leading to the characteristic elongated cell shape of motile cells with an actin semi-ring located close to the leading edge of cells. u-PAR effects on both chemotaxis and cytoskeleton were sensitive to pertussis toxin and, hence, possibly require G proteins. u-PAR effects are accompanied by a relocation of u-PAR, vitronectin receptor (VNR) vβ3, β1 integrin subunit, and Src tyrosine kinase to the leading membrane of migrating cells. In conclusion, our data show that pro-u-PA, via binding to u-PAR, controls a signaling pathway, regulated by tyrosine kinases and possibly G proteins, leading to cell cytoskeleton reorganization and cell migration.

The receptor for advanced glycation end products mediates the chemotaxis of rabbit smooth muscle cells

Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 463-472 ◽  
Author(s):  
T. Higashi ◽  
H. Sano ◽  
T. Saishoji ◽  
K. Ikeda ◽  
Y. Jinnouchi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Advanced Glycation End Products ◽  
Muscle Cells ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals The Immune Tolerance Role of the HMGB1-RAGE Axis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 564
Author(s):  
Haruki Watanabe ◽  
Myoungsun Son
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Lupus Erythematosus ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Chromatin Binding ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Extracellular Milieu

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.

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